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1.
PLoS One ; 19(9): e0310524, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39298444

RESUMO

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an inherited disease, the common variant caused by a Pi*Z mutation in the SERPINA1 gene. Pi*Z AAT increases the risk of pulmonary emphysema and liver disease. Berberine (BBR) is a nature dietary supplement and herbal remedy. Emerging evidence revealed that BBR has remarkable liver-protective properties against various liver diseases. In the present study, we investigated the therapeutic effects and toxicities of BBR in Pi*Z hepatocytes and Pi*Z transgenic mice. METHODS: Huh7.5 and Huh7.5Z (which carries the Pi*Z mutation) cells were treated with different concentrations of BBR for 48 hours. MTT was performed for cell viability assay. Intracellular AAT levels were evaluated by western blot. In vivo studies were carried out in wild type, native phenotype AAT (Pi*M), and Pi*Z AAT transgenic mice. Mice were treated with 50 mg/kg/day of BBR or solvent only by oral administration for 30 days. Western blot and liver histopathological examinations were performed to evaluate therapeutic benefits and liver toxicity of BBR. RESULTS: BBR reduced intracellular AAT levels in Huh7.5Z cells, meanwhile, no Pi*Z-specific toxicity was observed. However, BBR did not reduce liver AAT load but significantly potentiated liver inflammation and fibrosis accompanying the activation of unfolded protein response and mTOR in Pi*Z mice, but not in wild type and Pi*M mice. CONCLUSIONS: BBR exacerbated liver inflammation and fibrosis specifically in Pi*Z mice. This adverse effect may be associated with the activation of unfolded protein response and mTOR. This study implicates that BBR should be avoided by AATD patients.


Assuntos
Berberina , Cirrose Hepática , Camundongos Transgênicos , alfa 1-Antitripsina , Animais , Berberina/farmacologia , Camundongos , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/metabolismo , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/induzido quimicamente , Modelos Animais de Doenças , Serina-Treonina Quinases TOR/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatite/patologia , Hepatite/metabolismo , Hepatite/tratamento farmacológico , Hepatite/etiologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos
2.
Hepatol Commun ; 8(10)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39298568

RESUMO

BACKGROUND: In recent years, the use of immune checkpoint inhibitors (ICIs) has become a cornerstone in cancer treatment. However, this has also resulted in the emergence of immune-related adverse events, notably ICI hepatitis, posing a significant clinical challenge. While steroids are the primary treatment, there are increasing cases of steroid-refractory ICI hepatitis. Our objective is to investigate the management of ICI hepatitis and its response to steroid treatment. METHODS: PubMed/MEDLINE, EMBASE, and CENTRAL databases were searched in July 2023 based on keywords including ICIs (anti-Programmed cell death protein 1/Programmed Death-Ligand 1, anti-CTLA-4, and anti-LAG3) and hepatitis. RESULTS: A total of 4358 studies were screened, and 44 studies were included in this systematic review. One thousand eight hundred fifty-six patients with ICI hepatitis were included (grade 1-2: 31.7%, grade 3-4: 56.0%, and unknown: 12.3%) with 1184 patients who received corticosteroid treatment. The duration of treatment and dosage varied considerably across the studies. Mycophenolate mofetil was the predominant agent used in 68 out of 82 cases (82.9%), followed by infliximab and azathioprine. A summary estimate of the proportion of steroid-refractory hepatitis in a random effects model was 16% (95% CI: 11%-23%). An estimated 40% (95% CI: 30%-51%) of patients of all patients with ICI hepatitis were rechallenged with an ICI, and of those rechallenged, there was an estimated 22% (95% CI: 15%-30%) recurrence. CONCLUSIONS: Corticosteroids are the primary treatment for ICI hepatitis, with mycophenolate mofetil used as a secondary option for steroids-refractory cases. Current practices mostly rely on expert consensus, highlighting the need for further research to validate and optimize these treatments, particularly for steroid-resistant cases.


Assuntos
Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Corticosteroides/uso terapêutico , Hepatite/tratamento farmacológico , Hepatite/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Resistência a Medicamentos , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos
3.
Pan Afr Med J ; 48: 44, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39280832

RESUMO

This is the case of a 25-year-old patient, with the notion of unprotected sexual relations with multiple partners consulted for cholestatic icterus with pruritus evolving for 2 months. The general examination found an intense mucocutaneous icterus. The examination of the lymph nodes revealed multiple lymph nodes. A thoracic-abdominal-pelvic scanner showed peri-portal edema and adenopathies above and below the diaphragm without suspicious lesions. Biologically, there was acute cytolysis with ASAT at 1612IU/L, ALAT at 1506IU/L, and icteric cholestasis, the acute viral serologies and other autoantibodies were all negative. Given the presence of adenopathy and sexual risk factors, a syphilis serology was requested and was positive: a TPHA at 2560UI/L, and a VDRL at 1/32 UI/L. A liver biopsy was performed, which showed the presence, on immunohistochemistry, of anti-treponemal-pallidum antibodies. After eliminating all etiologies of cytolytic hepatitis, we retained the diagnosis of syphilitic hepatitis. Therapeutically, we started a treatment based on ceftriaxone 2g/dl with spectacular biological improvement at H48 of the beginning of treatment.


Assuntos
Antibacterianos , Hepatite , Sífilis , Humanos , Adulto , Sífilis/diagnóstico , Sífilis/complicações , Masculino , Hepatite/etiologia , Hepatite/diagnóstico , Hepatite/microbiologia , Antibacterianos/administração & dosagem , Doença Aguda , Ceftriaxona/administração & dosagem , Biópsia , Colestase/etiologia , Colestase/diagnóstico
4.
Recurso na Internet em Inglês, Espanhol, Francês, Português | LIS - Localizador de Informação em Saúde | ID: lis-49754

RESUMO

Antecipando o Dia Mundial de Combate à Hepatite (28 de julho), a Organização Pan-Americana da Saúde (OPAS) está incentivando os países a expandirem o acesso ao teste e tratamento para hepatite viral, que afeta mais de dez milhões de pessoas nas Américas, das quais apenas 23% são diagnosticadas.


Assuntos
Hepatite , Acessibilidade aos Serviços de Saúde , Organização Pan-Americana da Saúde/organização & administração
5.
Environ Int ; 190: 108937, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39126729

RESUMO

Human adenovirus (HAdV) type F41 has been identified as a possible cause of the non-A-to-E hepatitis outbreak. This study uses wastewater monitoring to track HAdV F40 and F41, supporting clinical investigations and providing insights into the pathogen's role in the outbreak. Given the limited clinical monitoring in Sweden of HAdV-F40/41, this approach also helps estimate the true infection burden of this pathogen during the outbreak. This study developed three qPCR assays for the hexon, penton, and fiber genes of HAdV F40 and F41. The hexon assay was F41-specific, while the fiber assay detected multiple HAdV-F strains. Comprehensive monitoring of HAdV-F40/41 levels in Stockholm's wastewater was conducted over 1.5 years, capturing the period before, during, and after the outbreak. A significant infection wave was observed in spring 2022, with strains beyond lineage 2 contributing to the outbreak. Moreover, simultaneous SARS-CoV-2 surveillance revealed that HAdV-F infections peaked at different times from COVID-19, but the HAdV-F wave aligned with the relaxation of pandemic restrictions. These findings offer valuable insights for future HAdV-F investigations and confirm its role in the non-A-to-E hepatitis outbreak.


Assuntos
Adenovírus Humanos , Surtos de Doenças , Águas Residuárias , Suécia/epidemiologia , Adenovírus Humanos/genética , Adenovírus Humanos/isolamento & purificação , Humanos , Águas Residuárias/virologia , Hepatite/epidemiologia , Hepatite/virologia , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/virologia , SARS-CoV-2/genética
6.
J Math Biol ; 89(3): 29, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012511

RESUMO

The paper presents an approach for overcoming modeling problems of typical life science applications with partly unknown mechanisms and lacking quantitative data: A model family of reaction-diffusion equations is built up on a mesoscopic scale and uses classes of feasible functions for reaction and taxis terms. The classes are found by translating biological knowledge into mathematical conditions and the analysis of the models further constrains the classes. Numerical simulations allow comparing single models out of the model family with available qualitative information on the solutions from observations. The method provides insight into a hierarchical order of the mechanisms. The method is applied to the clinics for liver inflammation such as metabolic dysfunction-associated steatohepatitis or viral hepatitis where reasons for the chronification of disease are still unclear and time- and space-dependent data is unavailable.


Assuntos
Simulação por Computador , Modelos Biológicos , Humanos , Fígado Gorduroso , Inflamação/imunologia , Conceitos Matemáticos , Hepatite Viral Humana , Hepatite
7.
Clin Res Hepatol Gastroenterol ; 48(7): 102421, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39002816

RESUMO

BACKGROUND: Spermine oxidase (SMOX), an inducible enzyme involved in the catabolic pathway of polyamine, was found to be upregulated in hepatocellular carcinoma and might be an important oncogene of it in our previous studies. This study attempted to further investigate its relationship with liver inflammation and fibrosis both in vitro and in vivo. METHODS: The effect of SMOX inhibition on LPS-induced inflammatory response in mouse liver cell line AML12 was validated by using small interfering RNA or SMOX inhibitor MDL72527. Western blotting and immunofluorescence were utilized to verify whether LPS could induce ß-catenin to transfer into the nucleus and whether it could be reversed by interfering with the expression of SMOX or using SMOX inhibitor. Then, the SMOX inhibitor MDL72527 and SMOX knockout mice were used to verify the hypothesis above in vivo. RESULTS: The expression of SMOX could be induced by LPS in AML12 cells. The inhibition of SMOX could inhibit LPS-induced inflammatory response in AML12 cells. LPS could induce ß-catenin transfer from cytoplasm to nucleus, while SMOX downregulation or inhibition could partially reverse this process. In vivo intervention with SMOX inhibitor MDL72527 or SMOX knockout mice could significantly improve the damage of liver function, reduce intrahepatic inflammation, inhibit the nuclear transfer of ß-catenin in liver tissue, and alleviate carbon tetrachloride-induced liver fibrosis in mice. CONCLUSION: SMOX can promote the inflammatory response and fibrosis of hepatocytes. It provides a new therapeutic strategy for hepatitis and liver fibrosis, inhibiting early liver cancer.


Assuntos
Cirrose Hepática , Oxirredutases atuantes sobre Doadores de Grupo CH-NH , Poliamina Oxidase , beta Catenina , Animais , Masculino , Camundongos , beta Catenina/metabolismo , Hepatite/etiologia , Hepatite/metabolismo , Lipopolissacarídeos , Cirrose Hepática/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Putrescina/análogos & derivados , Transdução de Sinais
11.
J Immunother Cancer ; 12(7)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969522

RESUMO

BACKGROUND: Immune-related hepatitis (irHepatitis) is a relatively common immune-related adverse event (irAE) of checkpoint inhibitors. Often, it responds well to steroids; however, in refractory cases, further therapy is needed. Anti-tumor necrosis factor (TNF) antibodies are used for management of multiple irAEs, but there are little data in irHepatitis. Here, we report on safety and efficacy of infliximab in 10 cases of steroid-refractory irHepatitis. METHODS: We retrospectively reviewed patients treated with infliximab for steroid-refractory grade ≥3 irHepatitis at the Department of Dermatology, University Hospital Zurich. The positive response to infliximab was defined as no further increase in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) above 50% than at the time of first infliximab infusion and control of irHepatitis without therapies other than steroids and infliximab. RESULTS: 10 patients with steroid-resistant irHepatitis grade ≥3 were treated with infliximab 5 mg/kg, of whom 7 (70%) responded positively. In two cases, the liver values increased over 50% before the irHepatitis could be controlled. In another case, therapies other than infliximab and steroids were given. At the median follow-up of 487 days, 90% of the patients demonstrated resolved irHepatitis without AST/ALT elevation following infliximab infusions. CONCLUSIONS: Treatment of irHepatitis with infliximab did not result in hepatotoxicity and led to long-lasting positive response in 9 of 10 of the cases. Further research is needed to evaluate the role of anti-TNF antibodies in management of irHepatitis.


Assuntos
Infliximab , Esteroides , Humanos , Infliximab/uso terapêutico , Infliximab/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Esteroides/uso terapêutico , Hepatite/tratamento farmacológico , Hepatite/etiologia , Adulto , Doença Hepática Induzida por Substâncias e Drogas/etiologia
12.
Clin Res Hepatol Gastroenterol ; 48(7): 102392, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38897557

RESUMO

OBJECTIVE: To evaluate the efficacy of rituximab (RTX)-containing therapy as first-line as well as rescue treatment for giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA). METHODS: This retrospective study recruited patients diagnosed with GCH-AHA and treated with conventional immunosuppressor regimens consisting of prednisone or RTX-containing regimes consisting of RTX and prednisone, with or without another immunosuppressor. The primary outcomes were the complete remission (CR) rate and time-period required for CR. The secondary outcomes included relapses and adverse events. RESULTS: Twenty patients (8 females and 12 males; age range 1-26 months), 15 receiving conventional regimens and 5 receiving RTX-containing regimens, were included. The CR rates were 73.3 % (11/15) and 100 % (5/5) in the conventional and RTX-containing groups, respectively. The time-period required for CR was significantly shorter in the RTX-containing group than in the conventional group (6 (3-8) versus 14 (5-25) months, P = 0.015). Relapses occurred in 30.8 % (4/13) of patients in the conventional group; all achieved CR after adding RTX. Relapses occurred in 40.0 % (2/5) of patients in the RTX-containing group; both achieved CR after adding intravenous immune globulins or tacrolimus. Transient low immunoglobulin and infections were recorded in both groups. Treatment withdrawal was achieved in 73.3 % (11/15) and 60.0 % (3/5) of patients receiving conventional and RTX-containing regimens after 36 (2-101) and 22 (4-41) months, respectively. Two patients in conventional group died of disease progression and infection. CONCLUSIONS: RTX-containing first-line therapy achieves CR of GCH-AHA more quickly than the conventional therapy. RTX is efficacious when added to rescue therapy.


Assuntos
Anemia Hemolítica Autoimune , Rituximab , Humanos , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Estudos Retrospectivos , Masculino , Feminino , Anemia Hemolítica Autoimune/tratamento farmacológico , Lactente , Pré-Escolar , Imunossupressores/uso terapêutico , Imunossupressores/administração & dosagem , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Quimioterapia Combinada , Resultado do Tratamento , Fatores Imunológicos/uso terapêutico , Fatores Imunológicos/administração & dosagem , Recidiva , Indução de Remissão , Hepatite/tratamento farmacológico , Hepatite/complicações
13.
Clin Res Hepatol Gastroenterol ; 48(7): 102407, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38936769

RESUMO

BACKGROUND AND AIMS: The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TCHep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TCHep group. METHODS: Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022. Patients were classified as known diagnosis, indeterminate hepatitis (IND-Hep), or TCHep (defined by liver biopsy with predominant CD8 T-cell inflammation or development of aplastic anemia). RESULTS: 124 patients were identified: 83 with known diagnoses, 16 with TCHep, and 25 with IND-Hep. Patients with TCHep had significantly increased median total bilirubin levels (7.5 mg/dL (IQR 6.8-8.9) vs 1.5 mg/dL (IQR 1.0-3.6), p < 0.0001), soluble interleukin-2 receptor levels (4512 IU/mL (IQR 4073-5771) vs 2997 IU/mL (IQR 1957-3237), p = 0.02), and percent of CD8+ T-cells expressing perforin (14.5 % (IQR 8.0-20.0) vs 1.0 % (IQR 0.8-1.0), p = 0.004) and granzyme (37.5 % (IQR 15.8-54.8) vs 4.0 % (IQR 2.5-5.5), p = 0.004) compared to IND-Hep patients. Clinical flow cytometry showed that TCHep patients had significantly increased percent CD8+ T cells (29.0 % (IQR 24.5-33.5) vs 23.6 % (IQR 19.8-25.8), p = 0.04) and HLA-DR+ (16.0 % (IQR 14.5-24.5) vs 2.7 (1.8-5.3), p < 0.001) compared to IND-Hep patients indicative of increase in CD8+ T cells that are activated. CONCLUSIONS: Peripheral blood clinical immune studies demonstrate increased markers of CD8 T-cell activation, proliferation, and cytotoxic function for TCHep patients. These readily available immune function labs can be used to help distinguish patients with TCHep from those with other causes. This provides a non-invasive tool for early detection of potential TCHep before progression to liver failure.


Assuntos
Linfócitos T CD8-Positivos , Humanos , Estudos Retrospectivos , Criança , Masculino , Feminino , Pré-Escolar , Linfócitos T CD8-Positivos/imunologia , Falência Hepática Aguda/imunologia , Falência Hepática Aguda/sangue , Adolescente , Hepatite/imunologia , Hepatite/sangue , Ativação Linfocitária , Lactente , Receptores de Interleucina-2/sangue , Granzimas/sangue
14.
J Clin Gastroenterol ; 58(7): 635-639, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38896421

RESUMO

Syphilitic hepatitis is a very rare presentation of syphilis infection, characterized by inflammation of the liver due to the invasion of hepatic tissue by the bacterium Treponema pallidum. This review article provides an in-depth analysis of the existing body of information pertaining to syphilitic hepatitis. The article primarily concentrates on key aspects such as the epidemiology, clinical manifestations, diagnostic methods, and therapeutic approaches associated with this condition. Despite its rarity, awareness of syphilitic hepatitis is vital for accurate diagnosis and appropriate intervention. The clinical presentations frequently exhibit similarities with many liver illnesses, hence presenting difficulties in making an accurate diagnosis. Common symptoms include fatigue, stomach pain, and jaundice. Diagnostic procedures encompass the use of serological assays, including rapid plasma reagin (RPR) and fluorescent treponemal antibody absorption (FTA-ABS), in conjunction with imaging modalities to evaluate hepatic engagement. The primary therapeutic approach is the prompt initiation of antibiotic therapy, with a particular emphasis on penicillin, to eradicate the causative bacterial infection and facilitate the restoration of liver function. Failure to swiftly manage this condition may result in substantial morbidity. In summary, syphilitic hepatitis is a very uncommon but medically relevant manifestation of syphilis infection. The significance of increased clinical suspicion, precise diagnostic techniques, and prompt antibiotic administration is emphasized in this review since these are crucial in reducing the potentially severe outcomes associated with this illness.


Assuntos
Antibacterianos , Hepatite , Sífilis , Treponema pallidum , Humanos , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Antibacterianos/uso terapêutico , Treponema pallidum/imunologia , Treponema pallidum/isolamento & purificação , Hepatite/diagnóstico , Hepatite/microbiologia , Hepatite/tratamento farmacológico
15.
BMJ Case Rep ; 17(6)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926121

RESUMO

SummaryUlcerative colitis (UC), a chronic inflammatory bowel disease, can cause extraintestinal manifestations (EIMs) in approximately 40% of individuals. This case report discusses the diagnostic procedure of a woman in her 20s who initially had non-specific symptoms. The patient underwent a thorough evaluation, which initially pointed towards tuberculosis (TB) due to necrotic lymphadenopathy and granulomatous hepatitis. However, no microbiological evidence of TB was found, and her symptoms worsened despite antitubercular therapy. The patient developed painful nodular-ulcerative skin lesions consistent with cutaneous polyarteritis nodosa (cPAN) on biopsy. Eventually, a definitive diagnosis of UC was made, revealing the true nature of her multisystemic manifestations. Cutaneous vasculitis, including leucocytoclastic vasculitis and cPAN, is a rare EIM of UC, with only five reported cases in the literature. This case report highlights the clinical implications of EIMs and contributes to the expanding knowledge of rare EIMs such as cPAN and granulomatous hepatitis.


Assuntos
Colite Ulcerativa , Hepatite , Poliarterite Nodosa , Humanos , Poliarterite Nodosa/diagnóstico , Poliarterite Nodosa/tratamento farmacológico , Poliarterite Nodosa/complicações , Feminino , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Hepatite/diagnóstico , Diagnóstico Diferencial , Granuloma/diagnóstico , Adulto , Antituberculosos/uso terapêutico
16.
Diagn Microbiol Infect Dis ; 110(1): 116371, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38838459

RESUMO

OBJECTIVES: Vibrio cholerae non-O1/non-O139 (NOVC) bacteremia is infrequently reported in Western countries and is associated with unfavorable outcome. PATIENT/METHOD: We describe here the case of a diabetic patient with hepatic cytolysis and NOVC bacteremia following an episode of diarrhea. RESULT: The patient was paucisymptomatic and had a favorable resolution with oral ciprofloxacin. CONCLUSION: NOVC should be systematically sought in stool samples, particularly in immunocompromised patients, due to an increased risk of infection occurrence.


Assuntos
Antibacterianos , Bacteriemia , Vibrio cholerae não O1 , Humanos , Bacteriemia/microbiologia , Bacteriemia/tratamento farmacológico , França/epidemiologia , Vibrio cholerae não O1/isolamento & purificação , Vibrio cholerae não O1/genética , Vibrio cholerae não O1/classificação , Antibacterianos/uso terapêutico , Masculino , Ciprofloxacina/uso terapêutico , Hepatite/microbiologia , Hepatite/complicações , Vibrioses/microbiologia , Vibrioses/diagnóstico , Vibrioses/tratamento farmacológico , Diarreia/microbiologia , Cólera/microbiologia , Cólera/complicações , Pessoa de Meia-Idade , Fezes/microbiologia , Idoso , Feminino
17.
Goiânia; SES/GO; 25 jun 2024. 1-15 p. map, graf.(Boletim epidemiológico: perfil epidemiológico de hepatites b e c no Estado de Goiás, 25, 6).
Monografia em Português | LILACS, CONASS, Coleciona SUS, SES-GO | ID: biblio-1563006

RESUMO

Boletim com o objetivo de demonstrar o perfil epidemiológico dos casos que foram notificados entre 2019 a 2023, apresentando os indicadores epidemiológicos e operacionais de relevância do estado, para fins de tomada de decisão em relação às ações do Programa para Eliminação das Hepatites Virais até 2030. Trata-se de uma análise de dados secundários obtidos do Sistema de Informação de Agravos de Notificações (SINAN), referentes aos casos diagnosticados e notificados, por município de residência entre 2019 e 2023 pelos serviços de saúde do Estado de Goiás


Bulletin with the aim of demonstrating the epidemiological profile of cases that were reported between 2019 and 2023, presenting epidemiological and operational indicators of relevance to the state, for decision-making purposes in relation to the actions of the Program for the Elimination of Viral Hepatitis by 2030. This is an analysis of secondary data obtained from the Notifiable Diseases Information System (SINAN), referring to cases diagnosed and notified, by municipality of residence between 2019 and 2023 by the health services of the State of Goiás


Assuntos
Humanos , Hepatite/epidemiologia , Hepatite C/diagnóstico , Hepatite C/mortalidade , Hepatite C/epidemiologia , Hepatite B/diagnóstico , Hepatite B/mortalidade , Hepatite B/epidemiologia
19.
Ren Fail ; 46(1): 2356023, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38785317

RESUMO

Glycyrrhizin (GL) has immunoregulatory effects on various inflammatory diseases including hepatitis and nephritis. However, the mechanisms underlying the anti-inflammatory effect of GL on renal inflammation are not fully understood. Hepatorenal syndrome (HRS) is a functional acute renal impairment that occurs in severe liver disease, and we found that kidney injury also occurs in Con A-induced experimental hepatitis in mice. We previously found that GL can alleviate Con A-induced hepatitis by regulating the expression of IL-25 in the liver. We wanted to investigate whether GL can alleviate Con A-induced nephritis by regulating IL-25. IL-25 regulates inflammation by modulating type 2 immune responses, but the mechanism by which IL-25 affects kidney disease remains unclear. In this study, we found that the administration of GL enhanced the expression of IL-25 in renal tissues; the latter promoted the generation of type 2 macrophages (M2), which inhibited inflammation in the kidney caused by Con A challenge. IL-25 promoted the secretion of the inhibitory cytokine IL-10 by macrophages but inhibited the expression of the inflammatory cytokine IL-1ß by macrophages. Moreover, IL-25 downregulated the Con A-mediated expression of Toll-like receptor (TLR) 4 on macrophages. By comparing the roles of TLR2 and TLR4, we found that TLR4 is required for the immunoregulatory effect of IL-25 on macrophages. Our data revealed that GL has anti-inflammatory effects on Con A-induced kidney injury and that the GL/IL-25/M2 axis participates in the anti-inflammatory process. This study suggested that GL is a potential therapeutic for protecting against acute kidney injury.


Assuntos
Modelos Animais de Doenças , Ácido Glicirrízico , Síndrome Hepatorrenal , Interleucinas , Rim , Macrófagos , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácido Glicirrízico/farmacologia , Ácido Glicirrízico/uso terapêutico , Síndrome Hepatorrenal/induzido quimicamente , Síndrome Hepatorrenal/tratamento farmacológico , Síndrome Hepatorrenal/metabolismo , Inflamação/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucinas/metabolismo , Rim/patologia , Rim/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Nefrite/tratamento farmacológico , Nefrite/metabolismo , Nefrite/etiologia , Nefrite/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Concanavalina A , Hepatite , Doença Hepática Induzida por Substâncias e Drogas/complicações , Doença Hepática Induzida por Substâncias e Drogas/metabolismo
20.
J Transl Med ; 22(1): 480, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773651

RESUMO

Inflammation plays a critical role in conditions such as acute liver failure, acute-on-chronic liver failure, and ischemia-reperfusion-induced liver injury. Various pathogenic pathways contribute to liver inflammation, involving inflammatory polarization of macrophages and Küpffer cells, neutrophil infiltration, dysregulation of T cell subsets, oxidative stress, and activation of hepatic stellate cells. While mesenchymal stromal cells (MSCs) have demonstrated beneficial properties, their clinical translation is limited by their cellular nature. However, MSC-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapeutic approach for immunomodulation. MSC-EVs naturally mirror their parental cell properties, overcoming the limitations associated with the use of MSCs. In vitro and in vivo preclinical studies have demonstrated that MSC-EVs replicate the beneficial effects of MSCs in liver injury. This includes the reduction of cell death and oxidative stress, improvement of hepatocyte function, induction of immunomodulatory effects, and mitigation of cytokine storm. Nevertheless, MSC-EVs face challenges regarding the necessity of defining consistent isolation methods, optimizing MSCs culture conditions, and establishing quality control measures for EV characterization and functional assessment. By establishing standardized protocols, guidelines, and affordable cost mass production, clinicians and researchers will have a solid foundation to conduct further studies, validate the therapeutic efficacy of MSC-EVs, and ultimately pave the way for their clinical implementation in acute liver injury.


Assuntos
Vesículas Extracelulares , Imunomodulação , Células-Tronco Mesenquimais , Pesquisa Translacional Biomédica , Vesículas Extracelulares/metabolismo , Humanos , Animais , Doença Aguda , Inflamação/patologia , Hepatite/imunologia , Hepatite/terapia
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